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1.
Comunidad (Barc., Internet) ; 22(3): 0-0, nov.-feb. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-195072

RESUMO

INTRODUCCIÓN: La pandemia ocasionada por el SARS-CoV-2 ha supuesto una reestructuración sin precedentes de la asistencia sanitaria y también de los centros de salud. OBJETIVO: Conocer las percepciones del personal médico del Centro de Salud Albaycín sobre la respuesta del equipo de Atención Primaria ante la pandemia de la COVID-19 en los meses de marzo y abril de 2020. MÉTODOS: Estudio cualitativo, observacional de orientación fenomenológica mediante entrevistas individuales. El ámbito de estudio es el Centro de Salud Albaycín. La saturación teórica determinó el tamaño de la muestra (la totalidad de la plantilla médica). Se llevó a cabo un análisis narrativo del contenido. RESULTADOS: Los discursos muestran seis categorías de análisis: organización de la toma de decisiones, características de la respuesta dada, mantenimiento de los pilares de la Atención Primaria, cualidades del equipo potenciadas, rol de la docencia y nuevas dinámicas generadas. Los resultados describen una respuesta adecuada, coordinada con la comunidad y anticipada a las directrices institucionales. La toma de decisiones ha sido consensuada y horizontal, potenciándose las cualidades del equipo. A pesar de las limitaciones, se ha mantenido la accesibilidad y la longitudinalidad. Durante la pandemia se ha visto afectada la calidad asistencial y la actividad docente. DISCUSIÓN: Un liderazgo transformacional, que refuerza el vínculo entre profesionales y fomenta la participación activa también de los residentes, permite una respuesta satisfactoria ante una situación emergente. Contar con la participación de la comunidad puede generar confianza en la organización y mejorar los resultados en salud


INTRODUCTION: The SARS-CoV-2 pandemic has brought about an unprecedented restructuring of healthcare and health centers. OBJECTIVES: Learn the perceptions of medical staff from Albayzín Health Centre regarding the Primary Care team's response to the COVID-19 pandemic in March and April 2020. METHODS: Qualitative, observational study with a phenomenological approach conducted by means of individual interviews. The scope of the study is Albaycín Health Centre. The theoretical saturation determined sample size (the entire medical staff). Content was analysed in narrative terms. RESULTS: Conversations revealed six categories of analysis: organization of the decision-making process, characteristics of the response provided, maintaining the cornerstones of Primary Care, enhanced team qualities, role of teaching and new dynamics generated. The results report an adequate response, which was coordinated with the community and anticipated institutional guidelines. Decision-making was consensual and horizontal, which enhanced the team's qualities. Despite the limitations, accessibility and longitudinal configuration have been maintained. Both the quality of care and teaching have been affected during the pandemic. DISCUSSION: Transformational leadership, which strengthens the bond between professionals and encourages residents to participate actively, facilitates a satisfactory response to an emerging situation. Having the community participate can build trust in the organization and improve health outcomes


Assuntos
Humanos , Infecções por Coronavirus/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Vírus da SARS/patogenicidade , Planejamento de Instituições de Saúde/organização & administração , Pessoal de Saúde/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Técnicas de Apoio para a Decisão
2.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-48017

RESUMO

O Ministério da Saúde informa que no último sábado (09/01), foi notificado, por meio do Centro de Informações Estratégicas e Resposta de Vigilância em Saúde (Cievs), sobre a identificação pelo Ministério da Saúde do Japão de uma nova cepa variante do vírus SARS-CoV-2 em quatro viajantes que chegaram a Tóquio vindos do Brasil.


Assuntos
Coronavirus , Brasil/epidemiologia , Vírus da SARS
3.
JCI Insight ; 6(1)2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427208

RESUMO

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross-SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection.


Assuntos
Anticorpos Neutralizantes/farmacologia , Imunidade Inata/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/uso terapêutico , /fisiopatologia , Cricetinae , Reações Cruzadas , Epitopos , Humanos , Imunidade Inata/imunologia , Imunoglobulina G/genética , Imunoglobulina G/uso terapêutico , Mesocricetus , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Engenharia de Proteínas , Receptores Fc/imunologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Células THP-1 , Carga Viral/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
4.
Int J Med Sci ; 18(3): 763-767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437211

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19's during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age. Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.


Assuntos
/epidemiologia , Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , /imunologia , Adulto , /terapia , Feminino , Humanos , Recém-Nascido , Exposição Materna , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/terapia , Complicações Infecciosas na Gravidez/virologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença
5.
Elife ; 102021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393462

RESUMO

Coronavirus entry is mediated by the spike protein that binds the receptor and mediates fusion after cleavage by host proteases. The proteases that mediate entry differ between cell lines, and it is currently unclear which proteases are relevant in vivo. A remarkable feature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the presence of a multibasic cleavage site (MBCS), which is absent in the SARS-CoV spike. Here, we report that the SARS-CoV-2 spike MBCS increases infectivity on human airway organoids (hAOs). Compared with SARS-CoV, SARS-CoV-2 entered faster into Calu-3 cells and, more frequently, formed syncytia in hAOs. Moreover, the MBCS increased entry speed and plasma membrane serine protease usage relative to cathepsin-mediated endosomal entry. Blocking serine proteases, but not cathepsins, effectively inhibited SARS-CoV-2 entry and replication in hAOs. Our findings demonstrate that SARS-CoV-2 enters relevant airway cells using serine proteases, and suggest that the MBCS is an adaptation to this viral entry strategy.


Assuntos
Organoides/virologia , Sistema Respiratório/virologia , Glicoproteína da Espícula de Coronavírus/química , Internalização do Vírus , Motivos de Aminoácidos , Animais , Fusão Celular , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Vírus da SARS/química , Vírus da SARS/fisiologia , Serina Endopeptidases , Células Vero
6.
Nat Commun ; 12(1): 6, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397903

RESUMO

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , /imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , /diagnóstico , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Análise em Microsséries/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes de Neutralização , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Artigo em Inglês | PAHO-IRIS | ID: phr-53189

RESUMO

To the Editor, During the past quarter of a century and following the global explosion in access to scientific literature, systematic reviews have become an excellent way to inform decisions with summaries of the effects of interventions, and to learn about their impact under different conditions or among populations. Systematic reviews play a key role in ensuring that policy decisions are informed by research. Local and national governments as well as international health organizations now regularly commission and request that systematic reviews inform policy decisions. [...]


Assuntos
Revisão Sistemática , Infecções por Coronavirus , Coronavirus , Infecções por Coronavirus , Hidroxicloroquina , Vírus da SARS , Betacoronavirus
8.
BMC Bioinformatics ; 22(1): 18, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413085

RESUMO

BACKGROUND: The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels. RESULTS: In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection. CONCLUSIONS: H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at: http://www.zhounan.org/h2v .


Assuntos
/metabolismo , Infecções por Coronavirus/metabolismo , Bases de Dados Genéticas , Bases de Dados de Proteínas , Síndrome Respiratória Aguda Grave/metabolismo , Interface Usuário-Computador , /genética , /virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Proteômica , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia
9.
FASEB J ; 35(1): e21197, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33368679

RESUMO

SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CLpro ) and papain-like protease (PLpro ) into 16 nonstructural proteins (nsps). PLpro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in the C-terminus of ubiquitin and of protein interferon-stimulated gene 15 (ISG15) with recognition motif of RLRGG. Alone or together with SARS unique domain (SUD), PLpro can stabilize an E3 ubiquitin ligase, the ring-finger, and CHY zinc-finger domain-containing 1 (RCHY1), through domain interaction, and thus, promote RCHY1 to ubiquitinate its target proteins including p53. However, a dilemma appears in terms of PLpro roles. On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state. This mini-review analyzes the dilemma and provides a snapshot on how the viral PLpro smartly manages its roles to avoid its simultaneously contradictory actions, which could shed lights on possible strategies to deal with SARS-CoV-2 infections.


Assuntos
/virologia , Vírus da SARS/fisiologia , Síndrome Respiratória Aguda Grave/virologia , /imunologia , /genética , Genes Virais , Interações Hospedeiro-Patógeno , Humanos , Terapia de Alvo Molecular , NF-kappa B/metabolismo , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/terapia , Especificidade por Substrato , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas Virais/metabolismo , Replicação Viral
10.
Comput Biol Med ; 128: 104123, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33260034

RESUMO

The ongoing COVID-19 pandemic caused by the coronavirus, SARS-CoV-2, has already caused in excess of 1.25 million deaths worldwide, and the number is increasing. Knowledge of the host transcriptional response against this virus and how the pathways are activated or suppressed compared to other human coronaviruses (SARS-CoV, MERS-CoV) that caused outbreaks previously can help in the identification of potential drugs for the treatment of COVID-19. Hence, we used time point meta-analysis to investigate available SARS-CoV and MERS-CoV in-vitro transcriptome datasets in order to identify the significant genes and pathways that are dysregulated at each time point. The subsequent over-representation analysis (ORA) revealed that several pathways are significantly dysregulated at each time point after both SARS-CoV and MERS-CoV infection. We also performed gene set enrichment analyses of SARS-CoV and MERS-CoV with that of SARS-CoV-2 at the same time point and cell line, the results of which revealed that common pathways are activated and suppressed in all three coronaviruses. Furthermore, an analysis of an in-vivo transcriptomic dataset of COVID-19 patients showed that similar pathways are enriched to those identified in the earlier analyses. Based on these findings, a drug repurposing analysis was performed to identify potential drug candidates for combating COVID-19.


Assuntos
Antivirais , Bases de Dados de Ácidos Nucleicos , Reposicionamento de Medicamentos , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Transcriptoma , /tratamento farmacológico , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/genética
11.
J Med Virol ; 93(2): 741-754, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32936465

RESUMO

Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.


Assuntos
/biossíntese , Infecções por Coronavirus/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , /virologia , Camelus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Cricetulus , Modelos Animais de Doenças , Humanos , Macaca mulatta , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , /imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de Subunidades , Vacinas Sintéticas/biossíntese , Vacinas de Partículas Semelhantes a Vírus/biossíntese
12.
J Mol Med (Berl) ; 99(1): 93-106, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33269412

RESUMO

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild-to-moderate upper respiratory tract diseases, such as the common cold, pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common-and least harmful-ones were discovered in the 1960s and cause a common cold. Others, more dangerous, identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the severe acute respiratory syndrome (the so-called SARS), which appeared in China in November 2002, the coronavirus 2012 (2012-nCoV) cause of the Middle Eastern respiratory syndrome (MERS) from coronavirus, which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new coronavirus strain was reported in Wuhan, China, identified as a new coronavirus beta strain ß-CoV from group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.


Assuntos
/genética , /virologia , China , Infecções por Coronavirus/classificação , Infecções por Coronavirus/genética , Infecções por Coronavirus/metabolismo , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/classificação , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Vírus da SARS/classificação , Vírus da SARS/genética , Vírus da SARS/metabolismo , /genética , /metabolismo
13.
Influenza Other Respir Viruses ; 15(1): 7-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32844604

RESUMO

To inform seroepidemiological studies, we characterized the IgG- responses in COVID-19 patients against the two major SARS-CoV-2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID-19 sera collected up to 85 days post-symptom onset and 230 non-COVID-19 sera, including 27 SARS sera from 2003. Although the average SARS-CoV-2 S and N-IgG titers were comparable, N-responses were more variable among individuals. S- and N-assay specificity tested with non-COVID-19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross-reactive potential and its' more consistent frequency of detection compared to N.


Assuntos
Anticorpos Antivirais/sangue , /imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Reações Cruzadas , Humanos , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Vírus da SARS/imunologia
14.
Eur J Pharmacol ; 890: 173659, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33131637

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of 2019 novel coronavirus disease (COVID-19), is currently spreading around the world. The WHO declared on January 31 that the outbreak of SARS-CoV-2 was a public health emergency. SARS-Cov-2 is a member of highly pathogenic coronavirus group that also consists of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Although respiratory tract lesions were regarded as main manifestation of SARS-Cov-2 infection, gastrointestinal lesions were also reported. Similarly, patients with SARS-CoV and MERS-CoV were also observed. Common gastrointestinal symptoms of patients mainly included diarrhea, vomiting and abdominal pain. Gastrointestinal lesions could be used as basis for early diagnosis of patients, and at the same time, controlling gastrointestinal lesions better facilitated to cut off the route of fecal-oral transmission. Hence, this review summarizes the characteristics and mechanism of gastrointestinal lesions caused by three highly pathogenic human coronavirus infections including SARS-CoV, MERS-CoV, as well as SARS-CoV-2. Furthermore, it is expected to gain experience from gastrointestinal lesions caused by SARS-CoV and MERS-CoV infections in order to be able to better relieve SARS-CoV-2 epidemic. Targetin gut microbiota to regulate the process of SARS-CoV-2 infection should be a concern. Especially, the application of nanotechnology may provide help for further controlling COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Gastroenteropatias/etiologia , Coronavírus da Síndrome Respiratória do Oriente Médio , Vírus da SARS , Animais , Humanos
15.
Eur J Pharmacol ; 890: 173656, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33086029

RESUMO

Angiotensin-converting enzyme 2 (ACE2) has been recognized as a potential entry receptor for SARS-CoV-2 infection. Binding of SARS-CoV-2 to ACE2 allows engagement with pulmonary epithelial cells and pulmonary infection with the virus. ACE2 is an essential component of renin-angiotensin system (RAS), and involved in promoting protective effects to counter-regulate angiotensin (Ang) II-induced pathogenesis. The use of angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEIs) was implicitly negated during the early phase of COVID-19 pandemic, considering the role of these antihypertensive agents in enhancing ACE2 expression thereby promoting the susceptibility to SARS-CoV-2. However, no clinical data has supported this assumption, but indeed evidence demonstrates that ACEIs and ARBs, besides their cardioprotective effects in COVID-19 patients with cardiovascular diseases, might also be beneficial in acute lung injuries by preserving the ACE2 function and switching the balance from deleterious ACE/Ang II/AT1 receptor axis towards a protective ACE2/Ang (1-7)/Mas receptor axis.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina , /metabolismo , Animais , Humanos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Vírus da SARS , Síndrome Respiratória Aguda Grave
16.
J Mol Graph Model ; 102: 107778, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33099199

RESUMO

COVID-19 caused by SARS-CoV-2 have become a global pandemic with serious rate of fatalities. SARS-CoV and MERS-CoV have also caused serious outbreak previously but the intensity was much lower than the ongoing SARS-CoV-2. The main infectivity factor of all the three viruses is the spike glycoprotein. In this study we have examined the intrinsic dynamics of the prefusion, lying state of trimeric S protein of these viruses through Normal Mode Analysis using Anisotropic Network Model. The dynamic modes of the S proteins of the aforementioned viruses were compared by root mean square inner product (RMSIP), spectral overlap and cosine correlation matrix. S proteins show homogenous correlated or anticorrelated motions among their domains but direction of Cα atom among the spike proteins show less similarity. SARS-CoV-2 spike shows high vertically upward motion of the receptor binding motif implying its propensity for binding with the receptor even in the lying state. MERS-CoV spike shows unique dynamical motion compared to the other two S protein indicated by low RMSIP, spectral overlap and cosine correlation value. This study will guide in developing common potential inhibitor molecules against closed state of spike protein of these viruses to prevent conformational switching from lying to standing state.


Assuntos
Coronavírus da Síndrome Respiratória do Oriente Médio/química , Vírus da SARS/química , Glicoproteína da Espícula de Coronavírus/química , /virologia , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Pandemias , Conformação Proteica , Domínios Proteicos , Estrutura Quaternária de Proteína
18.
Proteomics ; 21(2): e2000246, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33111431

RESUMO

The genome of coronaviruses, including SARS-CoV-2, encodes for two proteases, a papain like (PLpro ) protease and the so-called main protease (Mpro ), a chymotrypsin-like cysteine protease, also named 3CLpro or non-structural protein 5 (nsp5). Mpro is activated by autoproteolysis and is the main protease responsible for cutting the viral polyprotein into functional units. Aside from this, it is described that Mpro proteases are also capable of processing host proteins, including those involved in the host innate immune response. To identify substrates of the three main proteases from SARS-CoV, SARS-CoV-2, and hCoV-NL63 coronviruses, an LC-MS based N-terminomics in vitro analysis is performed using recombinantly expressed proteases and lung epithelial and endothelial cell lysates as substrate pools. For SARS-CoV-2 Mpro , 445 cleavage events from more than 300 proteins are identified, while 151 and 331 Mpro derived cleavage events are identified for SARS-CoV and hCoV-NL63, respectively. These data enable to better understand the cleavage site specificity of the viral proteases and will help to identify novel substrates in vivo. All data are available via ProteomeXchange with identifier PXD021406.


Assuntos
/virologia , Coronavirus Humano NL63/enzimologia , Fragmentos de Peptídeos/análise , Vírus da SARS/enzimologia , Proteínas Virais/metabolismo , /metabolismo , Células Cultivadas , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Fator de Iniciação 4G em Eucariotos/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Pulmão/metabolismo , Pulmão/virologia , Especificidade por Substrato
19.
J Virol Methods ; 288: 114013, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33166547

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended in the characterization of the SARS-CoV replication/transcription machinery. Until recently, a pure and highly active preparation of SARS-CoV recombinant RNA synthesis machinery was not available, impeding target-based high throughput screening of drug candidates against this viral family. The current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic revealed a new pathogen whose RNA synthesis machinery is highly (>96 % aa identity) homologous to SARS-CoV. This phylogenetic relatedness highlights the potential use of conserved replication enzymes to discover inhibitors against this significant pathogen, which in turn, contributes to scientific preparedness against emerging viruses. Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. The screening of a small (1520 compounds) chemical library of FDA-approved drugs demonstrates the robustness of our assay and will allow to speed-up drug discovery against the SARS-CoV-2.


Assuntos
Corantes Fluorescentes , Ensaios de Triagem em Larga Escala , RNA Viral , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/genética , Antivirais/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/normas , Humanos , Concentração Inibidora 50 , RNA Mensageiro/genética , Moldes Genéticos
20.
Cells ; 9(12)2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302501

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.


Assuntos
/química , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Vírus da SARS/metabolismo , Glicoproteína da Espícula de Coronavírus/química , /metabolismo , Sítios de Ligação , /virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Simulação de Dinâmica Molecular , Estrutura Terciária de Proteína , Vírus da SARS/genética , /isolamento & purificação , Glicoproteína da Espícula de Coronavírus/metabolismo
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